Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

LEUPRORELIN ACETATE

NFPA

PRODUCT USE

Antineoplastic (hormonal) in the treatment of prostatic carcinoma, the palliative
treatment of advanced prostatic cancer and for the treatment of children with central
precocious puberty. Synthetic nonapeptide agonist analogue of gonadorelin (LH- RH -
luteinising hormone release hormone).

SYNONYMS

C59-H84-N16-O12.C2-H4-O2, "luteinizing hormone-releasing factor (pig), 6-D-leucine-9-(N-
ethyl-", "luteinizing hormone-releasing factor (pig), 6-D-leucine-9-(N-ethyl-", "L-
prolinamide)-10-deglycinamide-, monoacetate (salt)", "L-prolinamide)-10-deglycinamide-,
monoacetate (salt)", "5-oxoPro-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-N-ethyl-L-prolinamide
acetate", "5-oxoPro-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-N-ethyl-L-prolinamide acetate", "6-D-
leucine-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinising hormone", "6-D-leucine-9-
(N-ethyl-L-prolinamide)-10-deglycinamide-luteinising hormone", "release factor",
"gonadotropin-releasing factor analogue", "gonadotropin releasing factor analogue", "LH-
releasing hormone analogue", "LH-releasing factor analogue", "LH-RF analogue", "LH-RH
analogue", "LH-RH/FSH-RH analogue", "LRF analogue", "LRH analogue", Abbott-43818,
Carcinil, Depo-Lupron, Enantone, Leuplin, "Leuprolide acetate", Lucrin, Lupron, "Lupron
Depot", Procrin, Prostap, TAP-144, TAP-144-SR, "hypothalmic neurohumoral hormone
analogue", "antineoplastic (hormonal)"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Although ingestion is not thought to produce harmful effects, the material may still be damaging to the health of the individual following ingestion, especially where pre-  existing organ (e.g. liver, kidney) damage is evident. Present definitions of harmful or toxic substances are generally based on doses producing mortality (death) rather than those producing morbidity (disease, ill-health). Gastrointestinal tract discomfort may produce nausea and vomiting. In an occupational setting however, ingestion of insignificant quantities is not thought to be cause for concern.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals.  

SKIN

  The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Open cuts, abraded or irritated skin should not be exposed to this material.  Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected.  

INHALED

  The material is not thought to produce adverse health effects or irritation of the respiratory tract (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting.  

CHRONIC HEALTH EFFECTS

  Limited evidence suggests that repeated or long-term occupational exposure may produce cumulative health effects involving organs or biochemical systems.  Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Prime symptom is breathlessness; lung shadows show on X-ray.  Exposure to small quantities may induce hypersensitivity reactions characterized by acute bronchospasm, hives (urticaria), deep dermal wheals (angioneurotic edema), running nose (rhinitis) and blurred vision . Anaphylactic shock and skin rash (non-thrombocytopenic purpura) may occur. An individual may be predisposed to such anti-body mediated reaction if other chemical agents have caused prior sensitization (cross-sensitivity).  Gonad-regulating hormones include the gonadotrophin glycoproteins and gonadorelin and its polypeptide analogues. They are usually administered parenterally to control the level of circulating sex hormones. These hormones stimulate the synthesis and releasing of follicle-stimulating hormone and luteinising hormone in the pituitary gland. Adverse effects of therapy include nausea and abdominal pain or discomfort, disturbances of the digestive system, hot flushes, mood change, nausea, vomiting, constipation, as well as headache and lightheadedness. Joint, bone and muscle pain may also appear. Other symptoms include muscle spasms, blurred vision, itching rashes, fever, chills, dry skin, hair loss,  changes in skin pigmentation and incontinence. Increased levels of circulating luteinising hormone may produce precocious puberty and enlarged breasts (gynaecomastia) and an increase in menstrual bleeding (menorrhagia).  Serious but comparatively rare health effects associated with treatment include angina, changes in heart rate, myocardial infarction and other potentially fatal cardiac effects, anaemia and other blood disorders, loss of sensation in the hands and feet, memory loss, blackouts and taste disorders.  Hypersensitivity reactions, including anaphylaxis, have been reported. Local and generalised skin rash has also been reported after chronic administration. Bronchospasm may also occur. Anaphylactoid reactions may include hypotension, fever, chills, mental confusion and wheezing.  Tumour flare has also been reported in the initial stages of treatment for cancer of the prostate. In addition, increased bone pain, a worsening of urinary symptoms with haematuria and urinary obstruction, and weakness and paraesthesia of the lower limbs may be present during treatment of patients with prostatic cancer. Anti-androgens may reduce these symptoms.  Reproductive system disorders including hot flushes, impotence, decreased libido, decreases in testicular size, atrophic genitalia and swollen or painful breasts have also been reported.  Evidence of teratogenic effects (often specific abnormalities of the musculoskeletal system) and foetotoxicity has been produced in several studies.  Exposure to the material may cause concerns for human fertility, on the basis that similar materials provide some evidence of impaired fertility in the absence of toxic effects, or evidence of impaired fertility occurring at around the same dose levels as other toxic effects, but which are not a secondary non-specific consequence of other toxic effects..  Based on experience with animal studies, there is a possibility that exposure to the material may result in toxic effects to the development of the fetus, at levels which do not cause significant toxic effects to the mother.  When administered to rabbits on day 6 of pregnancy, at test doses of 0.00024-0.024 mg/kg, leuprolide acetate produced a dose-related increase in foetal abnormalities. There was increased foetal mortality and decreased foetal weights with higher doses in rabbits and the highest dose  in rats. There was no evidence of mutagenic potential in mammalian bacterial systems (GensiaSicor).